Benzoxazole, benzothiazole and benzimidazole derivatives as fungicides

ABSTRACT

PCT No. PCT/GB92/01860 Sec. 371 Date Feb. 16, 1994 Sec. 102(e) Date Feb. 16, 1994 PCT Filed Oct. 12, 1992 PCT Pub. No. WO93/08180 PCT Pub. Date Apr. 29, 1993.    &lt;IMAGE&gt;  (I)  Fungicidal compounds having general formula (I) and stereoisomers thereof, in which A, B, C and D are independently H, halo, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl, C1-4 alkylthio, cyano, nitro, C1-4 haloalkyl, phenoxyobenzyl or benzyloxy, the phenyl moieties of any of the foregoing being optionally substituted with one or more of halo, C1-4 alkyl, C1-4 alkoxy, nitro or cyano; X is oxygen, sulphur or NR, in which R is H or C1-4 alkyl; and W is CH3O.CH=C.CO.CH3or CH3O.N=C.CONR1R2, in which R1 and R2 are independently H or methyl.

This application is A 391 of PCT/GB92/01860 filed Oct. 12, 1992.

This invention relates to benzoxazole, benzothiazole and benzimidazolederivatives useful as fungicides, to processes for preparing them, tofungicidal compositions containing them, and to methods of using them tocombat fungi, especially fungal infections of plants.

Certain fungicidal derivatives of benzoxazole, benzothiazole andbenzimidazole are described in EP-A-0299694.

According to the present invention there are provided heterocycliccompounds having the general formula (I), and stereoisomers thereof, inwhich A, B, C and D are independently H, halo (especially fluoro, chloroor bromo), C₁₋₄ alkyl (especially methyl or ethyl), C₂₋₄ alkenyl, C₂₋₄alkynyl, C₁₋₄ alkoxy (especially methoxy or ethoxy), C₁₋₄ alkylthio(especially methylthio or ethylthio), cyano, nitro, C₁₋₄ haloalkyl(especially trifluoromethyl), phenyl, phenoxy, benzyl or benzyloxy, thephenyl moleties of any of the foregoing being optionally substitutedwith one or more of halo, C₁₋₄ alkyl, C₁₋₄ alkoxy, nitro or cyano; X isoxygen, sulphur or NR, in which R is H or C₁₋₄ alkyl (especiallymethyl); and W is CH₃ O.CH═C.CO₂ CH₃ or CH₃ O.N═C.CONR¹ R²,in which R¹and R² are independently H or methyl.

Because the double bond of the W group is unsymmetrically substituted,the compounds of the invention may be obtained in the form of mixturesof (E)- and (Z)-geometric isomers. However, these mixtures can beseparated into individual isomers, and this invention embraces suchisomers and mixtures thereof in all proportions including those whichconsist substantially of the (Z)-isomer and those which consistsubstantially of the (E)-isomer. The (E)-isomer, in which the groups--OCH₃ and --C0₂ CH₃ or CONR¹ R² are on opposite sides of the olefinicbond of the W group, are the more fungicidally active and form apreferred embodiment of the invention.

Of particular interest are the compounds in which W is CH₃ O.Ch═C.CO₂CH₃ or CH₃ O.N═C.CONHCH₃, especially the (E)-isomers. Also of particularinterest are the compounds in which X is sulphur.

Typically A, B, C and D are independently H, halo, C₁₋₄ alkyl, C₁₋₄alkoxy, C₁₋₄ alkylthio, halo(C₁₋₄)alkyl, cyano or nitro; and usuallyeach of three of A, B, C and D is 5. More usually one of A and B is H,fluoro, chloro, bromo, methyl, ethyl, methoxy, ethoxy, methylthio,ethylthio, trifluoromethyl, cyano or nitro and the other is H, and eachof C and D is H.

In one aspect the invention provides a compound having the generalformula (I), especially its (E)-isomer, in which X is sulphur, W is CH₃O.CH═C.CO₂ CH₃ and A, B, C and D have the meanings given above.Typically one of A, B, C and D, usually A or B, is halo (especiallychloro), C₁₋₄ alkyl (especially methyl), C₁₋₄ alkoxy (especiallymethoxy), halo C₁₋₄ alkyl (especially trifluoromethyl), cyano or nitroand the others are H.

More particularly the invention provides the (E)-isomers of thecompounds in which X is sulphur, W is CH₃ O.CH═C.CO₂ CH₃, A is H orchloro and B, C and D are all H, i.e. the compounds (E)-methyl2-[2-(benzothiazol-2-yloxymethyl)phenyl]-3-methoxypropenoate and(E)-methyl2-[2-(4-chlorobenzothiazol-2-yloxymethyl)phenyl]-3-methoxypropenoate.Table I consists of 87 compounds of formula (I) in which the values ofA, B, C, D, W and X are given in the Table.

                                      TABLE I                                     __________________________________________________________________________    Compound                                                                      No.   A     B     C     D     X   W                                           __________________________________________________________________________    1     H     H     H     H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       2     Cl    H     H     H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       3     H     H     H     H     O   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       4     H     H     H     H     S   CH.sub.3 O.N═C.CONHCH.sub.3             5     H     H     H     H     O   CH.sub.3 O.N═C.CONHCH.sub.3             6     H     Cl    H     H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       7     H     H     Cl    H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       8     H     H     H     Cl    S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       9     CH.sub.3                                                                            H     H     H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       10    H     CH.sub.3                                                                            H     H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       11    CH.sub.3                                                                            H     H     H     O   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       12    H     CH.sub.3                                                                            H     H     O   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       13    CH.sub.3                                                                            H     H     H     S   CH.sub.3 O.N═C.CONHCH.sub.3             14    CH.sub.3 O                                                                          H     H     H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       15    H     CH.sub.3 O                                                                          H     H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       16    CH.sub.3 O                                                                          H     H     H     O   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       17    H     CH.sub.3 O                                                                          H     H     O   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       18    CH.sub.3 O                                                                          H     H     H     S   CH.sub.3 O.N═C.CONHCH.sub.3             19    H     H     H     H     NCH.sub.3                                                                         CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       20    Cl    H     H     H     S   CH.sub.3 O.N═C.CONHCH.sub.3             21    H     Cl    H     H     S   CH.sub.3 O.N═C.CONHCH.sub.3             22    H     H     Cl    H     S   CH.sub.3 O.N═C.CONHCH.sub.3             23    H     H     H     Cl    S   CH.sub.3 O.N═C.CONHCH.sub.3             24    F     H     H     H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       25    H     F     H     H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       26    H     H     F     H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       27    H     H     H     F     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       28    F     H     H     H     S   CH.sub.3 O.N═C.CONHCH.sub.3             29    H     F     H     H     S   CH.sub.3 O.N═C.CONHCH.sub.3             30    H     H     F     H     S   CH.sub.3 O.N═C.CONHCH.sub.3             31    H     H     H     F     S   CH.sub.3 O.N═C.CONHCH.sub.3             32    Br    H     H     H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       33    H     Br    H     H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       34    H     H     Br    H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       35    H     H     H     Br    S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       36    Br    H     H     H     S   CH.sub.3 O.N═C.CONHCH.sub.3             37    H     Br    H     H     S   CH.sub.3 O.N═C.CONHCH.sub.3             38    H     H     Br    H     S   CH.sub.3 O.N═C.CONHCH.sub.3             39    H     H     H     Br    S   CH.sub.3 O.N═C.CONHCH.sub.3             40    CN    H     H     H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       41    H     CN    H     H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       42    H     H     CN    H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       43    H     H     H     CN    S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       44    CN    H     H     H     S   CH.sub.3 O.N═C.CONHCH.sub.3             45    H     CN    H     H     S   CH.sub.3 O.N═C.CONHCH.sub.3             46    H     H     CN    H     S   CH.sub.3 O.N═C.CONHCH.sub.3             47    H     H     H     CN    S   CH.sub.3 O.N═C.CONHCH.sub.3             48    NO.sub.2                                                                            H     H     H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       49    H     NO.sub.2                                                                            H     H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       50    H     H     NO.sub.2                                                                            H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       51    H     H     H     NO.sub.2                                                                            S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       52    NO.sub.2                                                                            H     H     H     S   CH.sub.3 O.N═C.CONHCH.sub.3             53    H     NO.sub.2                                                                            H     H     S   CH.sub.3 O.N═C.CONHCH.sub.3             54    H     H     NO.sub.2                                                                            H     S   CH.sub.3 O.N═C.CONHCH.sub.3             55    H     H     H     NO.sub.2                                                                            S   CH.sub.3 O.N═C.CONHCH.sub.3             56    CH.sub.3 CH.sub.2 O                                                                 H     H     H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       57    H     CH.sub.3 CH.sub.2 O                                                                 H     H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       58    H     H     CH.sub.3 CH.sub.2 O                                                                 H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       59    H     H     H     CH.sub.3 CH.sub.2 O                                                                 S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       60    CH.sub.3 CH.sub.2 O                                                                 H     H     H     S   CH.sub.3 O.N═C.CONHCH.sub.3             61    H     CH.sub.3 CH.sub.2 O                                                                 H     H     S   CH.sub.3 O.N═C.CONHCH.sub.3             62    H     H     CH.sub.3 CH.sub.2 O                                                                 H     S   CH.sub.3 O.N═C.CONHCH.sub.3             63    H     H     H     CH.sub.3 CH.sub.2 O                                                                 S   CH.sub.3 O.N═C.CONHCH.sub.3             64    CH.sub.3 S                                                                          H     H     H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       65    H     CH.sub.3 S                                                                          H     H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       66    H     H     CH.sub.3 S                                                                          H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       67    H     H     H     CH.sub.3 S                                                                          S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       68    CH.sub.3 S                                                                          H     H     H     S   CH.sub.3 O.N═C.CONHCH.sub.3             69    H     CH.sub.3 S                                                                          H     H     S   CH.sub.3 O.N═C.CONHCH.sub.3             70    H     H     CH.sub.3 S                                                                          H     S   CH.sub.3 O.N═C.CONHCH.sub.3             71    H     H     H     CH.sub.3 S                                                                          S   CH.sub.3 O.N═C.CONHCH.sub.3             72    CH.sub.3 CH.sub.2                                                                   H     H     H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       73    H     CH.sub.3 CH.sub.2                                                                   H     H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       74    H     H     CH.sub.3 CH.sub.2                                                                   H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       75    H     H     H     CH.sub.3 CH.sub.2                                                                   S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       76    CH.sub.3 CH.sub.2                                                                   H     H     H     S   CH.sub.3 O.N═C.CONHCH.sub.3             77    H     CH.sub.3 CH.sub.2                                                                   H     H     S   CH.sub.3 O.N═C.CONHCH.sub.3             78    H     H     CH.sub.3 CH.sub.2                                                                   H     S   CH.sub.3 O.N═C.CONHCH.sub.3             79    H     H     H     CH.sub.3 CH.sub.2                                                                   S   CH.sub.3 O.N═C.CONHCH.sub.3             80    CF.sub.3                                                                            H     H     H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       81    H     CF.sub.3                                                                            H     H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       82    H     H     CF.sub.3                                                                            H     S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       83    H     H     H     CF.sub.3                                                                            S   CH.sub.3 O.CH═C.CO.sub.2 CH.sub.3       84    CF.sub.3                                                                            H     H     H     S   CH.sub.3 O.N═C.CONHCH.sub.3             85    H     CF.sub.3                                                                            H     H     S   CH.sub.3 O.N═C.CONHCH.sub.3             86    H     H     CF.sub.3                                                                            H     S   CH.sub.3 O.N═C.CONHCH.sub.3             87    H     H     H     CF.sub.3                                                                            S   CH.sub.3 O.N═C.CONHCH.sub.3             __________________________________________________________________________

                                      TABLE II                                    __________________________________________________________________________    Table II gives melting points and selected proton NMR data obtained at        270 MHz for certain compounds described in Table I. Chemical shifts are       measured at 20° C. in ppm from tetramethylsilane and                   deuterochloroform was                                                         used as solvent, unless otherwise stated. The following abbreviations are     used:                                                                                s = singlet  m = multiplet                                                    d = doublet  br = broad                                                       t = triplet  ppm = parts per million                                   Compound                                                                            Melting                                                                 No    Point (°C.)                                                                  Proton NMR Data (δ)                                         __________________________________________________________________________    1     107-108                                                                             3.69(3H, s); 3.82(3H, s); 5.48(2H, s); 7.16-7.28(2H, m);                      7.31-7.44(3H, m); 7.55-7.73(3H, m); 7.59.sup.+ (1H, s) ppm.       2     110-112                                                                             3.69(3H, s); 3.84(3H, s); 5.57(2H, s); 7.07-7.28(2H, m);                      7.31-7.45(3H, m); 7.45-7.66(2H, m); 7.58.sup.+ (1H, s) ppm.       4     104-105                                                                             2.92(3H, d); 3.95(3H, s); 5.47(2H, s); 6.76(1H, brs);                         7.18-7.29(2H, m); 7.37(1H, t); 7.40-7.51(2H, m);                              7.51-7.72(3H, m) ppm.                                             6     Oil   3.70(3H, s); 3.83(3H, s); 5.48(2H, s); 7.11-7.33(2H, m);                      7.33-7.43(2H, m); 7.49-7.71(2H, m); 7.59.sup.+ (1H, s);                       7.68(1H, d) ppm.                                                  __________________________________________________________________________     .sup.+ Chemical shift of singlet from olefinic proton on methoxypropenoat     group (ppm from tetramethylsilane).                                      

The compounds of the invention of formula (I) can be prepared by thesteps illustrated in Schemes 1 to 4 . Throughout the Schemes thevariables A, B, C, D, W and X have the values given above, Y isHO.CH═C.CO₂ CH₃ or HO.N═C.CONR¹ R², Z is CH₂ CO₂ CH₃ or CH₂.CONR¹ R², Qis CO.CO₂ CH₃ or CO.CONR¹ R², Ph is phenyl and L is a leaving group suchas halo or CH₃ SO₂.O.

In Scheme 1, compounds of the invention of formula (I) can be preparedby coupling hydroxy compounds of formula (II) with benzyl compounds offormula (III) in the presence of a base (such as silver carbonate), in aconvenient solvent (such as toluene) at a temperature of 20°-110° C.

In an alternative approach, shown in Scheme 2, compounds of theinvention of formula (I) can be prepared by coupling benzyl alcohols offormula (V) with compounds of formula (IV) in the presence of a base(such as sodium hydride, sodium carbonate or silver carbonate), in aconvenient solvent (such as toluene or N,N dimethylformamide) at atemperature of 20°-110° C.

In Scheme 3, compounds of the invention of formula (I) can be preparedby methylation of the compounds of formula (VI) with a compound CH₃ L inthe presence of a convenient base (such as sodium hydride or potassiumcarbonate). The compounds of formula (VI) can be conveniently preparedfrom the substituted phenylacetic acid derivatives (VII) by methodsknown in the literature (see, for example, EP-A-0178826, EP-A-0254426,EP-A-0278595, EP-A-0299694 and EP-A-0398692).

In a further alternative approach, shown in Scheme 4, compounds of theinvention of formula (I) can be prepared from substitutedphenylglyoxylic acid derivatives (VIII) by treatment with theappropriate reagent. For example, when W is CH₃ O.CH═C.CO₂ CH₃ compoundsof formula (I) can be prepared by treating the derivative (VIII) withthe Wittig reagent Ph₃ P═CH.OCH₃ and when W is CH₃ O.N═C.CONR¹ R²compounds of formula (I) can be prepared by reacting the derivative(VIII) with a substituted hydroxylamine H₂ N.OCH₃. The intermediatecompounds (VII) and (VIII) can be prepared by the same couplingreactions as those described in Schemes 1 and 2.

The compounds of formula (I) in which W is CH₃ O.N═C.CONR¹ R² can alsobe prepared from the corresponding compounds (I) in which W is CH₃O.N═C.CO₂ H by methods set out in the literature and in other ways asdescribed in EP-A-0398692.

In a further aspect, the present invention provides processes forpreparing compounds of formula (I).

The compounds are active fungicides and may be used to control one ormore of the following pathogens: Pyricularia oryzae on rice and wheatand other Pyricularia spp. on other hosts; Puccinia recondita, Pucciniastriiformis and other rusts on wheat, Puccinia hordei, Pucciniastriiformis and other rusts on barley, and rusts on other hosts e.g.turf, rye, coffee, pears, apples, peanuts, sugar beet, vegetables andornamental plants; Erysiphe graminis (powdery mildew) on barley, wheat,rye and turf and other powdery mildews on various hosts such asSphaerotheca macularis on hops, Sphaerotheca fuliginea on cucurbits(e.g. cucumber), Podosphaera leucotricha on apple and Uncinula necatoron vines; Cochliobolus spp., Helminthosporium spp., Drechslera spp.(Pyrenophora spp.), Rhynchosporium spp., Septoria spp. (includingMycosphaerella graminicola and Leptosphaeria nodorum),Pseudocercosporella herpotrichoides and Gaeumannomyces graminis oncereals (e.g. wheat, barley, rye), turf and other hosts; Cercosporaarachidicola and Cercosporidium personarum on peanuts and otherCercospora species on other hosts, for example, sugar beet, bananas,soya beans and rice; Botrytis cinerea (grey mould) on tomatoes,strawberries, vegetables, vines and other hosts and other Botrytis spp.on other hosts; Alternaria spp. on vegetables (e.g. cucumber), oil-seedrape, apples, tomatoes, cereals (e.g. wheat) and other hosts; Venturiaspp. (including Venturia inaequalis (scab)) on apples, pears, stonefruit, tree nuts and other hosts; Cladosporium spp. on a range of hostsincluding cereals (e.g. wheat); Monilinia spp. on stone fruit, tree nutsand other hosts; Didymella spp. on tomatoes, turf, wheat and otherhosts; Phoma spp. on oil-seed rape, turf, rice, potatoes, wheat andother hosts; Aspergillus spp. and Aureobasidium spp. on wheat, lumberand other hosts; Ascochyta spp. on peas, wheat, barley and other hosts;Plasmopara viticola on vines; other downy mildews such as Bremialactucae on lettuce, Peronospora spp. on soybeans, tobacco, onions andother hosts, Pseudoperonospora humuli on hops and Pseudoperonosporacubensis on cucurbits; Pythium spp. on turf and other hosts;Phytophthora infestans on potatoes and tomatoes and other Phytophthoraspp. on vegetables, strawberries, avocado, pepper, ornamentals, tobacco,cocoa and other hosts; Thanatephorus cucumeris on rice and turf andother Rhizoctonia species on various hosts such as wheat and barley,vegetables, cotton and turf; Sclerotinia spp. on turf, peanuts, oil-seedrape and other hosts; Sclerotium spp. on turf, peanuts and other hosts;Colletotrichum spp. on a range of hosts including turf, coffee andvegetables; Laetisaria fuciformis on turf; Mycosphaerella spp. onbanana, peanut, citrus, pecan, papaya and other hosts; Diaporthe spp. oncitrus, soybean, melon, pear, lupin and other hosts; Elsinoe spp. oncitrus, vines, olives, pecans, roses and other hosts; Pyrenopeziza spp.on oil-seed rape and other hosts; Oncobasidium theobromae on cocoacausing vascular streak dieback; Fusarium spp., Typhula spp.,Microdochium nivale, Ustilago spp., Urocystis spp., Tilletia spp., andClaviceps purpurea on a variety of hosts but particularly wheat, barley,turf and Baize; Ramularia spp. on sugar beet and other hosts;post-harvest diseases particularly of fruit (e.g. Pencillium digitalumand P. italicum and Trichoderma viride on oranges, Colletotrichum musaeand Gloeosporium musarum on bananas and Botrytis cinerea on grapes);other pathogens on vines, notably Eutypa lata, Guignardia bidwellii,Phellinus igniarus, Phomopsis viticola, Pseudopezicula tracheiphila andStereum hirsutum; other pathogens on lumber, notably Cephaloascusfragrans, Ceratocystis spp., Ophiostoma piceae, Penicillium spp.,Trichoderma pseudokoningii, Triehoderma viride Trichoderma harzianum,Aspergillus niger, Leptographium lindberyl and Aureobasidium pullulans;and fungal vectors of vital diseases e.g. Polymyxa graminis on cerealsas the vector of barley yellow mosaic virus (BYMV).

Some of the compositions show a broad range of activities against fungiin vitro.

Further, some of the compositions may be active as seed dressingsagainst pathogens including Fusarium spp., Septoria spp., Tillella spp.,(e.g. bunt, a seed-borne disease of wheat), Ustilago spp. andHelminthosporium spp. on cereals, Rhizoctonia solani on cotton andPyricularia oryzae on rice.

The compounds may move acropetally/locally in plant tissue. Moreover,the compounds may be volatile enough to be active in the vapour phaseagainst fungi on the plant.

The invention therefore provides a method of combating fungi whichcomprises applying to a plant, to a seed of a plant or to the locus ofthe plant or seed a fungicidally effective amount of a compound ashereinbefore defined, or a composition containing the same.

The compounds may be used directly for agricultural purposes but aremore conveniently formulated into compositions using a carrier ordiluent. The invention thus provides fungicidal compositions comprisinga compound as hereinbefore defined and an acceptable carrier or diluenttherefor. It is preferred that all compositions, both solid and liquidformulations, comprise 0.0001 to 95%, more preferably 1 to 85%, forexample 1 to 25% or 25 to 60%, of a compound as hereinbefore defined.

When applied the foliage of plants, the compounds of the invention areapplied at rates of 0.1 g to 10 kg, preferably 1 g to 8kg, morepreferably 10 g to 4kg, of active ingredient (invention compound) perhectare.

When used as seed dressings, the compounds of the invention are used atrates of 0.0001 g (for example 0.001 g or 0.05 g) to 10 g, preferably0.005 g to 8 g, more preferably 0.005 g to 4 g, of active ingredient(invention compound) per kilogram of seed.

The compounds can be applied in a number of ways. For example, they canbe applied, formulated or unformulated, directly to the foliage of aplant, to seeds or to other medium in which plants are growing or are tobe planted, or they can be sprayed on, dusted on or applied as a creamor paste formulation, or they can be applied as a vapour or as slowrelease granules.

Application can be to any part of the plant including the foliage,stems, branches or roots, or to soil surrounding the roots, or to theseed before it is planted, or to the soil generally, to paddy water orto hydroponic culture systems. The invention compounds may also beinjected into plants or sprayed onto vegetation using electrodynamicspraying techniques or other low volume methods.

The term "plant" as used herein includes seedlings, bushes and trees.Furthermore, the fungicidal method of the invention includespreventative, protectant, prophylactic, systemic and eradicanttreatments.

The compounds are preferably used for agricultural and horticulturalpurposes in the form of a composition. The type of composition used inany instance will depend upon the particular purpose envisaged.

The compositions may be in the form of dustable powders or granulescomprising the active ingredient (invention compound) and a soliddiluent or carrier, for example, fillers such as kaolin, bentonire,kieselguhr, dolomite, calcium carbonate, talc, powdered magnesia,fuller's earth, gypsum, diatomaceous earth and china clay. Such granulescan be preformed granules suitable for application to the soil withoutfurther treatment. These granules can be made either by impregnatingpellets of filler with the active ingredient or by pelleting a mixtureof the active ingredient and powdered filler. Compositions for dressingseed may include an agent (for example, a mineral oil) for assisting theadhesion of the composition to the seed; alternatively the activeingredient can be formulated for seed dressing purposes using an organicsolvent (for example, N-methylpyrrolidone, propylene glycol orN,N-dimethylformamide). The compositions may also be in the form ofwater dispersible powders or water dispersible granules comprisingwetting or dispersing agents to facilitate the dispersion in liquids.The powders and granules may also contain fillers and suspending agents.

The compositions may also be in the form of soluble powders or granules,or in the form of solutions in polar solvents.

Soluble powders may be prepared by mixing the active ingredient with awater-soluble salt such as sodium bicarbonate, sodium carbonate,magnesium sulphate or a polysaccharide, and a wetting or dispersingagent to improve water dispersibility/solubility. The mixture may thenbe ground to a fine powder. Similar compositions may also be granulatedto form water-soluble granules. Solutions may be prepared by dissolvingthe active ingredient in polar solvents such as ketones, alcohols andglycol ethers. These solutions may contain surface active agents toimprove water dilution and prevent crystallisation in a spray tank.

Emulsifiable concentrates or emulsions may be prepared by dissolving theactive ingredient in an organic solvent optionally containing a wettingor emulsifying agent and then adding the mixture to water which may alsocontain a wetting or emulsifying agent. Suitable organic solvents arearomatic solvents such as alkylbenzenes and alkylnaphthalenes, ketonessuch as cyclohexanone and methylcyclohexanone, chlorinated hydrocarbonssuch as chlorobenzene and trichlorethane, and alcohols such as benzylalcohol, furfuryl alcohol, butanol and glycol ethers.

Aqueous suspension concentrates of largely insoluble solids may beprepared by ball or bead milling with a dispersing agent with asuspending agent included to stop the solid settling.

Compositions to be used as sprays may be in the form of aerosols whereinthe formulation is held in a container under pressure of a propellant,e.g. fluorotrichloromethane or dichlorodifluoromethane.

The invention compounds can be mixed in the dry state with a pyrotechnicmixture to form a composition suitable for generating in enclosed spacesa smoke containing the compounds.

Alternatively, the compounds may be used in micro-encapsulated form.They may also be formulated in biodegradable polymeric formulations toobtain a slow, controlled release of the active substance.

By including suitable additives, for example additives for improving theuptake, distribution, adhesive power and resistance to rain on treatedsurfaces, the different compositions can be better adapted for variousutilities. Other additives may be included to improve the biologicalefficacy of the various formulations. Such additives can be surfaceactive materials to improve the wetting and retention on surfacestreated with the formulation and also the uptake and mobility of theactive material, or additionally can include oil based spray additives,for example, certain mineral oil and natural plant oil (such as soyabean and rape seed oil) additives, or blends of them with otheradjuvants.

The invention compounds can be used as mixtures with fertilisers (e.g.nitrogen-, potassium- or phosphorus-containing fertilisers).Compositions comprising only granules of fertiliser incorporating, forexample coated with, a compound of formula (I) are preferred. Suchgranules suitably contain up to 25% by weight of the compound. Theinvention therefore also provides a fertiliser composition comprising afertiliser and the compound of general formula (I) or a salt or metalcomplex thereof.

Water dispersible powders, emulsifiable concentrates and suspensionconcentrates will normally contain surfactants, e.g. a wetting agent,dispersing agent, emulsifying agent or suspending agent. These agentscan be cationic, anionic or non-ionic agents.

Suitable cationic agents are quaternary ammonium compounds, for example,cetyltrimethylammonium bromide. Suitable anionic agents are soaps, saltsof aliphatic monoesters of sulphuric acid (for example, sodium laurylsulphate), and salts of sulphonated aromatic compounds (for example,sodium dodecylbenzenesulphonate, sodium, calcium or ammoniumlignosulphonate, butylnaphthalene sulphonate, and a mixture of sodiumdiisopropyl- and triisopropylnaphthalene sulphonates).

Suitable non-ionic agents are the condensation products of ethyleneoxide with fatty alcohols such as oleyl or cetyl alcohol, or with alkylphenols such as octyl- or nonylphenol and octylcresol. Other non-ionicagents are the partial esters derived from long chain fatty acids andhexitol anhydrides, alkyl glucosides, polysaccharides and the lecithinsand the condensation products of the said partial esters with ethyleneoxide. Suitable suspending agents are hydrophilic colloids (for example,polyvinylpyrrolidone and sodium carboxymethylcellulose), and swellingclays such as bentonitc or attapulgite.

Compositions for use as aqueous dispersions or emulsions are generallysupplied in the form of a concentrate containing a high proportion ofthe active ingredient, the concentrate being diluted with water beforeuse. These concentrates should preferably be able to withstand storagefor prolonged periods and after such storage be capable of dilution withwater in order to form aqueous preparations which remain homogeneous fora sufficient time to enable them to be applied by conventional sprayequipment. The concentrates may conveniently contain up to 95%, suitably1-85%, for example 1-25% or 25-60%, by weight of the active ingredient.After dilution to form aqueous preparations, such preparations maycontain varying amounts of the active ingredient depending upon theintended purpose, but an aqueous preparation containing 0.0001 to 10%,for example 0.005 to 10%, by weight of active ingredient may be used.

The compositions of this invention may contain other compounds havingbiological activity, e.g. compounds having similar or complementaryfungicidal activity or which possess plant growth regulating, herbicidalor insecticidal activity.

An additional fungicidal compound may be present in the composition ofthe invention. By including another fungicide, the resulting compositioncan have a broader spectrum of activity or a greater level of intrinsicactivity than the compound of general formula (I) alone. Further theother fungicide can have a synergistic effect on the fungicidal activityof the compound of general formula (I). Examples of fungicidal compoundswhich may be included in the composition of the invention are(±)-cis-1-(4--chlorophenyl)-2-(1H-1,2,4-triazol-1-yl)cycloheptanol,(2RS,3RS)-1-[3-(2-chlorophenyl)-2-(4-fluorophenyl)oxiran-2-ylmethyl]-1H-1,2,4-triazole,(RS)-1-aminopropylphosphonic acid,(RS)-4-(4-chlorophenyl)-2-phenyl-2-(1H-1,2,4-triazol-1-ylmethyl)butyronitrile,(Z)-N-but-2-enyloxymethyl-2-chloro-2',6'-diethylacetanilide,1-(2-cyano-2--methoxyiminoacetyl)-3-ethyl urea,3-(2,4-dichlorophenyl)-2-(1H-1,2,4-tri-azol-1-yl)quinazolin-4(3H)-one,4-(2,2-difluoro-1,3-benzodioxol-4-yl)pyrrole-3-carbonitrile,4-bromo-2-cyano-N,N-dimethyl-6-trifluoromethylbenzimidazole-1-sulphonamide,5-ethyl-5,8-dihydro-8-oxo(1,3)-dioxolacetamido] -γ-butyrolactone,N-(2-methoxy-5-pyridyl)-cyclopropane carboxamide, (E)-methyl2-[2-(6-(cyanophenoxy)pyrimidin-4-yloxy)phenyl]-3-methoxypropenoate,alanycarb, aldimorph, ampropylfos, anilazine, azaconazole, benalaxyl,benomyl, biloxazol, binapacryl, bitertanol, blasticidin S,bromuconazole, bupirimate, butenachlor, buthiobate, captafol, captan,carbendazim, carbendazim chlorhydrate, carboxin, chinomethionate,chlorbenzthiazone, chloroneb, chlorothalonil, chlorozolinate,clozylacon, copper containing compounds such as copper oxychloride,copper oxyquinolate, copper sulphate and Bordeaux mixture,cycloheximide, cymoxanil, cyproconazole, cyprofuram, di-2-pyridyldisulphide 1,1'-dioxide, dichlofluanid, dichlone, diclobutrazol,diclomezine, dicloran, didecyl dimethyl ammonium chloride,diethofencarb, difenoconazole, O,O-di-iso-propyl-S-benzyl thiophosphate,dimefluazole, dimetconazole, dimethomorph, dimethirimol, diniconazole,dinocap, dipyrithione, ditalimfos, dithianon, dodemorph, dodine,doguadine, edifenphos, epoxiconazole, etaconazole, ethirimol,ethoxyquin, ethyl(Z)-N-benzyl-N-([methyl(methyl-thioethylideneamino-oxycarbonyl)amino]thio)-β-alaninate,etridiazole, fenaminosulph, fenapanil, fenarimol, fenbuconazole,fenfuram, fenpiclonil, fenpropidin, fenpropimorph, fentin acetate,fentin hydroxide, ferbam, ferimzone, fluazinam, fluoroimide, flutolanil,flutriafol, flusilazole, folpet, fuberidazole, furalaxyl,furconazole-cis, guazatine, hexaconazole, hydroxyisoxazole, hymexazole,imazalil, imibenconazole, ipconazole, iprobenfos, iprodione, isopropanylbutyl carbamate, isoprothiolane, kasugamycin, mancozeb, maneb,mepanipyrim, mepronil, metalaxyl, methfuroxam, metiram, metiram-zinc,metsulfovax, myclobutanil, neoasozin, nickel dimethyldithiocarbamate,nitrothal-iso-propyl, nuarimol, ofurace, organomercury compounds,oxadixyl, oxolinic acid, oxycarboxin, pefurazoate, penconazole,pencycuron, phenazin oxide, phosetyl-Al, phosphorus acids, phthalide,polyoxin D, polyram, probenazole, prochloraz, procymidone, propamocarb,propamocarb hydrochloride, propiconazole, propineb, propionic acid,prothiocarb, pyracarbolid, pyrazophos, pyrifenox, pyroquilon, pyroxy#ur,pyrrolnitrin, quaternary ammonium compounds, quinconazole,quinomethionate, quintozene, rabenazole, sodium pentachlorophenate,streptomycin, sulphur, tebuconazole, techlofthalam, tecnazene,tetraconazole, thiabendazole, thicarbanil, thicyofen,2-(thiocyanomethylthio)benzothiazole, thiophanate-methyl, thiram,timibenconazole, tolclofos-methyl, tolylfluanid, triacetate salt of1,1'-iminodi(octamethylene)diguanidine, triadimefon, triadimenol,triazbutyl, triazoxide, tricyclazole, tridemorph, tri#orine,triflumizole, triticonazole, validamycin A, vapam, vinclozolin, zineband ziram. The compounds of general formula (I) can be mixed with soil,peat or other rooting media for the protection of plants againstseed-borne, soil-borne or foliar fungal diseases.

The following Examples illustrate the invention. Throughout theExamples, the term `ether` refers to diethyl ether, magnesium sulphatewas used to dry solutions, and.solutions were concentrated under reducedpressure. Reactions involving air or water sensitive intermediates wereperformed under an atmosphere of nitrogen and solvents were dried beforeuse, where appropriate. Unless otherwise stated, chromatography wasperformed on a column of silica gel as the stationary phase. Whereshown, infrared and NMR data are selective; no attempt is made to listevery absorption in all cases. ¹ H NMR spectra were recorded using CDCl₃-solutions unless otherwise stated. The following abbreviations are usethroughout:

    ______________________________________                                        NMR = nuclear magnetic resonance                                                                  m = multiplet                                             IR = infrared       br = broad                                                S = singlet         m.p. = melting point                                      d = doublet         ppm = parts per million                                   t = triplet                                                                   ______________________________________                                    

EXAMPLE 1

This Example illustrates the preparation of (E)-methyl2-[2-(benzo-thiazol-2-yloxymethyl)phenyl]-3-methoxypropenoate (Compound1 of Table I).

2-Hydroxybenzothiazole (1.56 g) and silver carbonate (2.91 g) were addedtoa solution of (E)-methyl 2-[2-(bromomethyl)phenyl]-3-methoxypropenoate(2.00 g) in dry toluene (40 ml). The mixture was heated and stirred at110° C. under a nitrogen atmosphere in the dark. After two hours, more(E)-methyl 2-[2-(bromomethyl)phenyl]-3-methoxypropenoate (1.00 g)wasadded to the cooled mixture and heating continued for a further fourhours.The cooled mixture was diluted with toluene (30 ml), filteredthrough HyfloSupercel filter aid and the filtrate concentrated underreduced pressure. The residue was dissolved in dichloromethane (40 ml)and washed with 2N sodium hydroxide solution (2 ×30 ml) and water (25ml). The dichloromethane solution was dried and concentrated underreduced pressure. Chromatography of the residue on silica gel (Merck 60)using ethyl acetate-n-hexane 1:3 as eluent afforded the title compoundas a colourles oil (0.71 g) which crystallised on standing.Recrystallisation from ether-n-hexane yielded a white powder (0.57 g,15.3%), m.p. 107°-108° C.; IR maxima (nujol mull): 1710, 1630 cm⁻¹ ; ¹ HNMR (CDCl₃, 270 MHz): δ3.69(3H,s), 3.82(3H,s) 5.48(2H,s),7.16-7.28(2H,m), 7.31-7.44(3H,m), 7.55-7.73(3H,m), 7.59(1H,s) ppm.

EXAMPLE 2

This Example illustrates the preparation of (E)-methyl2-[2-(4-chlorobenzothiazol-2-yloxymethyl)phenyl]-3-methoxypropenoate(Compound 2 of Table I).

(E)-methyl 2-[2-(bromomethyl)phenyl]-3-methoxypropenoate (2.00 g) wastreated with 4-chloro-2-hydroxybenzothiazole (1.95 g) and silvercarbonate(2.91 g) in dry toluene (45 ml) as described in Example 1. Thecrude product, obtained after work up as a brown oil (4.37 g), waschromatographed on silica gel (Merck 60) using ethyl acetate-N-hexane1:2,and then acetone-n-hexane 1:6.5, to afford the title compound as apale yellow gum (0.30 g) which crystallised on trituration withether-N-hexane to yield a light yellow powder (0.14 g, 5.1%) m.p.110°-112°C.; IR maxima (nujol mull): 1705, 1630 cm⁻¹ ; ¹ H NMR (CDCl₃,270 MHz):δ3.69(3H,s), 3.84(3H,s), 5.57(2H,s), 7.07-7.28(2H,m),7.31-7.45(3H,m), 7.45-7.66(2H,m), 7.58(1H,s) ppm.

EXAMPLE 3

This Example illustrates the preparation of (E)-N-methyl-O-methyl-2-[2-(benzothiazol-2-yloxymethyl)phenyl]oximinoacetamide(Compound4 of Table I).

Step 1

2-Hydroxybenzothiazole (0.5 g) and silver carbonate (0.91 g) were addedto a solution of (E)-methylO-methyl-2-[2-(bromomethyl)phenyl]oximinoacetate (2.10 g, prepared asdescribed in EP-A-0363818) in dry toluene (25 ml). The mixture washeated and stirred at 110° C. under a nitrogen atmosphere in the dark.After six hours, more 2-hydroxybenzothiazole (0.25g) and silvercarbonate (0.45 g) were added to the cooled mixture and heatingcontinued for a further six hours. The cooled reaction mixturewasfiltered through Hyflo Supercel filter aid and the liltrateconcentrated under reduced pressure. The brown oil (2.53 g) was purifiedby flash column chromatography on silica gel (Merck 60) using ethylacetate:n-hexane 2:7 to give (E)-methylO-methyl-2-[2-(benzothiazol-2-yloxymethyl)phenyl]oximinoacetate (0.16 g,20%) as a white powder, m.p. 93°-4° C.; ¹ H NMR (CDCl₃, 270 MHz):δ3.97(3H,s), 4.04(3H,s), 5.45(2H,s), 7.18-7.29(2H,m), 7.36(1H,t),7.40-7.54(2H,m), 7.58-7.74(3H,m) ppm; IR maxima (nujol mull): 1735 cm⁻¹.

Step 2

Methylamine gas was passed through a suspension of (E)-methylO-methyl-2-[2-benzothiazol-2-yloxymethyl)phenyl]oximinoacetate (0.119 g)in methanol, with stirring, for 15 minutes. The resulting clear solutionwas allowed to stand at room temperature for 0.5 hours. Removal of themethanol gave a white crystalline solid which on recrystallisation fromn-hexane/diethyl ether gave the title compound (0.100 g, 84%) as a whitecrystalline solid, m.p. 104°-5° C.; ¹ H NMR (CDCl₃, 270 MHz):δ2.92(3H,d), 3.95(3H,s), 5.47(2H,s), 6.76(1H,brs), 7.18-7.29(2H,m),7.37(1H,t), 7.40-7.51(2H,m), 7.51-7.72(3H,m) ppm; IR maxima (nujolmull): 1665 , 3330 cm⁻¹.

EXAMPLE 4

The compounds were tested against a variety of foliar fungal diseases ofplants. The technique employed was as follows.

The plants were grown in John Innes Potting Compost (No 1 or 2) in 4 cmdiameter minipots. The test compounds were formulated either by beadmilling with aqueous Dispersol T or as a solution in acetone oracetone/ethanol which was diluted to the required concentrationimmediately before use. The formulations (100 ppm active ingredient)were sprayed on to the foliage or applied to the roots of the plants inthe soil. The sprays were applied to maximum retention and the rootdrenches to a final concentration equivalent to approximately 40 ppma.i. in dry soil. Tween 20 was added to give a final concentration of0.05% when the sprays were applied to cereals.

For most of the tests the compounds were applied to the soil (roots) orto the foliage (by spraying) one or two days before the plant wasinoculated with the disease. An exception was the test on Erysiphegraminis in which the plants were inoculated 24 hours before treatment.Foliar pathogens were applied by spray as zoosporangial suspensions ontothe leaves of testplants. After inoculation, the plants were put into anappropriate environment to allow infection to proceed and then incubateduntil the disease was ready for assessment. The period betweeninoculation and assessment varied from four to fourteen days accordingto the disease and environment.

The disease level present (i.e. leaf area covered by activelysporulating disease) on each of the treated plants was recorded usingthe following assessment scale:

    ______________________________________                                         0 = 0% disease present                                                                        20 = 10.1-20% disease present                                 1 = 0.1-1% disease present                                                                    30 = 20.1-30% disease present                                 3 = 1.1-3% disease present                                                                    60 = 30.1-60% disease present                                 5 = 3.1-5% disease present                                                                    90 = 60.1-100% disease present                               10 = 5.1-10% disease present                                                  ______________________________________                                    

Each assessment was then expressed as a percentage of the level ofdisease present on the untreated control plants. This calculated valueis referredto as a POCO (Percentage of Control) value. An example of atypical calculation is as follows:

Disease level on untreated control =90

Disese level on treated plant =30 ##EQU1##

This calculated POCO value is then rounded to the nearest of the valuesin the 9-point assessment scale shown above. In this particular example,the POCO value would be rounded to 30. If the calculated POCO fallsexactly mid-way between two of the points, it is rounded to the lower ofthe two values.

The results are shown in Table III.

                  TABLE III                                                       ______________________________________                                        Compound No                                                                   of Table I                                                                              Pr     Egt    Sn   Po   Tc   Vi   Pv  Pil                           ______________________________________                                        1         90.sup.a                                                                             0.sup.a                                                                              10.sup.a                                                                           0.sup.a                                                                            30.sup.a                                                                           0.sup.a                                                                            0.sup.a                                                                           3.sup.a                       2         0*     0      0    0    0    0    0   0                             4         90     0      30   0    0    90   0   0                             6         5.sup.a                                                                              0.sup.a                                                                              0.sup.a                                                                            0.sup.a                                                                            0.sup.a                                                                            0.sup.a                                                                            0.sup.a                                                                           0.sup.a                       ______________________________________                                    

    ______________________________________                                        Key to Diseases                                                               ______________________________________                                        Pr   Puccinia recondita                                                                            Tc     Thanetophorus cucumeris                           Egt  Erysiphe graminis tritici                                                                     Vi     Venturia inaegualis                               Sn   Septoria nodorum                                                                              Pv     Plasmopara viticola                               Po   Pyricularia oryzae                                                                            Pil    Phytophthora infestans                                                        lycopersici                                       ______________________________________                                         ##STR2##

We claim:
 1. A compound having the general formula (I):and stereoisomersthereof, in which A, B, C and D are independently H, halo, C₁₋₄ alkyl,C₂₋₄ alkenyl, C₂₋₄ alkynyl, C₁₋₄ alkoxy, C₁₋₄ alkylthio, cyano, nitro,C₁₋₄ haloalkyl, phenyl, phenoxy, benzyl or benzyloxy, the phenylmoieties of any of the foregoing being optionally substituted with oneor more of halo, C₁₋₄ alkyl, C₁₋₄ alkoxy, nitro or cyano; X is oxygen,sulphur or NR, in which R is H or C₁₋₄ alkyl; and W is CH₃ CH═C.CO₂ CH₃or CH₃ O.N═C.CONR¹ R², in which R¹ and R² are independently H or methyl.2. A compound according to claim 1 in which W is CH₃ O.CH═C.CO₂ CH₃ orCH₃ O.N═C.CONHCH₃.
 3. The (E)-isomer of a compound according to claim 1.4. A compound according to claim 1 in which X is sulphur.
 5. A compoundaccording to claim 1 in which A, B, C and D are independently H, halo,C₁₋₄ alkyl, C₁₋₄ alkoxy, C₁₋₄ alkylthio, halo(C₁₋₄)alkyl, cyano ornitro.
 6. A compound according to claim 5 in which each of three of A,B, C and D is H.
 7. A compound according to claim 1 in which one of Aand B is H, fluoro, chloro, bromo, methyl, ethyl, methoxy, ethoxy,methylthio, ethylthio, trifluoromethyl, cyano or nitro, and the other isH, and each of C and D is H.
 8. A fungitidal composition comprising afungicidally effective amount of a compound according to claim 1 and afungicidally acceptable carrier or diluent therefor.
 9. A method ofcombating fungi which comprises applying to plants, to the seeds ofplants or to the locus of the plants or seeds, a fungicidally effectiveamount of a compound according to claim
 1. 10. A method of combattingfungi which comprises applying to plants, to the seeds of plants or tothe locus of the plants or seeds, a composition according to claim 8.